Do lutein, zeaxanthin, and macular pigment optical density differ with age or age-related maculopathy?

Background and aims Current age-related macular disease (ARMD) treatment includes antioxidant supplementation. Lutein (L) and zeaxanthin (Z) are antioxidants that make up macularpigment within the retina and may reduce the risk of developing ARMD. Ageing and smoking are leading risk factors for developing ARMD. We investigated differences in dietary, supplemental and retinal L and Z, and smoking habits in healthy younger eyes (HY), healthy older eyes (HO) and eyes with an early form of ARMD called age-related maculopathy (ARM). Methods HO, HY and ARM groups were assessed for dietary intakes of L and Z using food diaries. Smoking habits and self-administered quantities of L and Z were obtained via questionnaire. Retinal L and Z levels (macularpigmentopticaldensity, or MPOD) were determined using heterochromatic flicker photometry. Results No significant difference was demonstrated for dietary L and Z intake (?2 = 4.983, p = 0.083) or for MPOD between groups (F = 0.40, p = 0.67). There was a significant difference between the HY (mean ± sd: 1.20 ± 2.99), HO (4.51 ± 7.05) ARM groups (9.15 ± 12.28) for pack years smoked (?2 = 11.61, p = 0.03). Conclusions Our results do not support the theory that ARM develops as a result of L and Z deficiency. Higher pack years smoked may be a factor in disease development. Dietary and supplementary L and Z levels must be obtained when assessing MPOD between groups or over time

Giant negative magnetoresistance in semiconductors doped by multiply charged deep impurities

A giant negative magnetoresistance has been observed in bulk germanium doped with multiply charged deep impurities. Applying a magnetic field the resistance may decrease exponentially at any orientation of the field. A drop of the resistance as much as about 10000% has been measured at 6 T. The effect is attributed to the spin splitting of impurity ground state with a very large g-factor in the order of several tens depending on impurity.Comment: 4 pages, 4 figure

Application of the density dependent hadron field theory to neutron star matter

The density dependent hadron field (DDRH) theory, previously applied to isospin nuclei and hypernuclei is used to describe $\beta$-stable matter and neutron stars under consideration of the complete baryon octet. The meson-hyperon vertices are derived from Dirac-Brueckner calculations of nuclear matter and extended to hyperons. We examine properties of density dependent interactions derived from the Bonn A and from the Groningen NN potential as well as phenomenological interactions. The consistent treatment of the density dependence introduces rearrangement terms in the expression for the baryon chemical potential. This leads to a more complex condition for the $\beta$-equilibrium compared to standard relativistic mean field (RMF) approaches. We find a strong dependence of the equation of state and the particle distribution on the choice of the vertex density dependence. Results for neutron star masses and radii are presented. We find a good agreement with other models for the maximum mass. Radii are smaller compared to RMF models and indicate a closer agreement with results of non-relativistic Brueckner calculations.Comment: 28 pages, 11 figure

How phyllosilicate mineral structure affects fault strength in Mg-rich fault systems

The clay mineralogy of fault gouges has important implications for the frictional properties of faults, often identified as a major factor contributing to profound fault weakness. This work compares the frictional strength of a group of Mg‐rich minerals common in the Mg‐Al‐Si‐O compositional space (talc, saponite, sepiolite, and palygorskite) by conducting triaxial frictional tests with water or argon as pore fluid. The studied minerals are chemically similar but differ in their crystallographic structure. Results show that fibrous Mg‐rich phyllosilicates are stronger than their planar equivalents. Frictional strength in this group of minerals is highly influenced by strength of the atomic bonds, continuity of water layers within the crystals, and interactions of mineral surfaces with water molecules, all of which are dictated by crystal structure. The formation and stability of the minerals studied are mainly controlled by small changes in pore fluid chemistry, which can lead to significant differences in fault strength

Stopped-flow fluorimetry using voltage-sensitive fluorescent membrane probes

Australian Research Counci

The effect of nutritional supplementation on the multifocal electroretinogram in healthy eyes

BACKGROUND: Previous studies have demonstrated an increase in macular pigment optical density (MPOD) with lutein (L)-based supplementation in healthy eyes. However, not all studies have assessed whether this increase in MPOD is associated with changes to other measures of retinal function such as the multifocal ERG (mfERG). Some studies also fail to report dietary levels of L and zeaxanthin (Z). Because of the associations between increased levels of L and Z, and reduced risk of AMD, this study was designed to assess the effects of L-based supplementation on mfERG amplitudes and latencies in healthy eyes. METHODS: Multifocal ERG amplitudes, visual acuity, contrast sensitivity, MPOD and dietary levels of L and Z were assessed in this longitudinal, randomized clinical trial. Fifty-two healthy eyes from 52 participants were randomly allocated to receive a L-based supplement (treated group), or no supplement (non-treated group). RESULTS: There were 25 subjects aged 18-77 (mean age ± SD; 48 ± 17) in the treated group and 27 subjects aged 21-69 (mean age ± SD; 43 ± 16) in the non-treated group. All participants attended for three visits: visit one at baseline, visit two at 20 weeks and visit three at 40 weeks. A statistically significant increase in MPOD (F = 17.0, p ≤ 0.001) and shortening of mfERG ring 2 P1 latency (F = 3.69, p = 0.04) was seen in the treated group. CONCLUSIONS: Although the results were not clinically significant, the reported trend for improvement in MPOD and mfERG outcomes warrants further investigation

The oxysterol 27-hydroxycholesterol increases β-amyloid and oxidative stress in retinal pigment epithelial cells

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several pathological features including β-amyloid (Aβ) peptide accumulation, oxidative damage, and cell death. The causes of AD and AMD are not known but several studies suggest disturbances in cholesterol metabolism as a culprit of these diseases. We have recently shown that the cholesterol oxidation metabolite 27-hydroxycholesterol (27-OHC) causes AD-like pathology in human neuroblastoma SH-SY5Y cells and in organotypic hippocampal slices. However, the extent to which and the mechanisms by which 27-OHC may also cause pathological hallmarks related to AMD are ill-defined. In this study, the effects of 27-OHC on AMD-related pathology were determined in ARPE-19 cells. These cells have structural and functional properties relevant to retinal pigmented epithelial cells, a target in the course of AMD.</p> <p>Methods</p> <p>ARPE-19 cells were treated with 0, 10 or 25 μM 27-OHC for 24 hours. Levels of Aβ peptide, mitochondrial and endoplasmic reticulum (ER) stress markers, Ca²⁺homeostasis, glutathione depletion, reactive oxygen species (ROS) generation, inflammation and cell death were assessed using ELISA, Western blot, immunocytochemistry, and specific assays.</p> <p>Results</p> <p>27-OHC dose-dependently increased Aβ peptide production, increased levels of ER stress specific markers caspase 12 and gadd153 (also called CHOP), reduced mitochondrial membrane potential, triggered Ca²⁺dyshomeostasis, increased levels of the nuclear factor κB (NFκB) and heme-oxygenase 1 (HO-1), two proteins activated by oxidative stress. Additionally, 27-OHC caused glutathione depletion, ROS generation, inflammation and apoptotic-mediated cell death.</p> <p>Conclusions</p> <p>The cholesterol metabolite 27-OHC is toxic to RPE cells. The deleterious effects of this oxysterol ranged from Aβ accumulation to oxidative cell damage. Our results suggest that high levels of 27-OHC may represent a common pathogenic factor for both AMD and AD.</p

A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes: design and methodology [ISRCTN78467674]

BACKGROUND: Age-related macular disease is the leading cause of blind registration in the developed world. One aetiological hypothesis involves oxidation, and the intrinsic vulnerability of the retina to damage via this process. This has prompted interest in the role of antioxidants, particularly the carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye disease. METHODS: The aim of this randomised controlled trial is to determine the effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc, and copper on measures of visual function in people with and without age-related macular disease. Outcome measures are distance and near visual acuity, contrast sensitivity, colour vision, macular visual field, glare recovery, and fundus photography. Randomisation is achieved via a random number generator, and masking achieved by third party coding of the active and placebo containers. Data collection will take place at nine and 18 months, and statistical analysis will employ Student's t test. DISCUSSION: A paucity of treatment modalities for age-related macular disease has prompted research into the development of prevention strategies. A positive effect on normals may be indicative of a role of nutritional supplementation in preventing or delaying onset of the condition. An observed benefit in the age-related macular disease group may indicate a potential role of supplementation in prevention of progression, or even a degree reversal of the visual effects caused by this condition

Biomolecular simulations: From dynamics and mechanisms to computational assays of biological activity

Biomolecular simulation is increasingly central to understanding and designing biological molecules and their interactions. Detailed, physics‐based simulation methods are demonstrating rapidly growing impact in areas as diverse as biocatalysis, drug delivery, biomaterials, biotechnology, and drug design. Simulations offer the potential of uniquely detailed, atomic‐level insight into mechanisms, dynamics, and processes, as well as increasingly accurate predictions of molecular properties. Simulations can now be used as computational assays of biological activity, for example, in predictions of drug resistance. Methodological and algorithmic developments, combined with advances in computational hardware, are transforming the scope and range of calculations. Different types of methods are required for different types of problem. Accurate methods and extensive simulations promise quantitative comparison with experiments across biochemistry. Atomistic simulations can now access experimentally relevant timescales for large systems, leading to a fertile interplay of experiment and theory and offering unprecedented opportunities for validating and developing models. Coarse‐grained methods allow studies on larger length‐ and timescales, and theoretical developments are bringing electronic structure calculations into new regimes. Multiscale methods are another key focus for development, combining different levels of theory to increase accuracy, aiming to connect chemical and molecular changes to macroscopic observables. In this review, we outline biomolecular simulation methods and highlight examples of its application to investigate questions in biology. This article is categorized under: Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Free Energy Method